TP53 and PTEN mutations detected in 68% and 47% of ovarian and endometrial cancer samples respectively in a retrospective cohort.

Ovarian and endometrial cancers together account for nearly 10% of all female cancer-related deaths worldwide, with ovarian cancer being the deadliest gynecologic malignancy. We aimed to evaluate the diagnostic performance of genetic mutations and DNA methylation markers detected from cervicovaginal swabs for identifying ovarian and endometrial cancers. We conducted a retrospective multicenter cohort study including 238 women (127 ovarian/endometrial cancers; 111 benign controls) from three tertiary hospitals between 2018 and 2023. Targeted sequencing was performed for TP53, PTEN, BRCA1, and BRCA2; DNA methylation profiling was analyzed using quantitative methylation-specific PCR (qMSP). Logistic regression and ROC analyses assessed diagnostic accuracy. Survival was evaluated by Kaplan–Meier methods and Cox regression. TP53 and PTEN mutations were identified in 68% and 47% of cancer samples, respectively, versus Genetic and epigenetic alterations detectable in cervicovaginal swabs can accurately identify ovarian and endometrial cancers, demonstrating feasibility for non-invasive molecular triage. Incorporation of TP53 and PTEN sequencing with methylation profiling warrants further prospective investigation as a potential adjunct to upper-tract oncologic surveillance.